Diplomazia pontificia e Comunità internazionale nel contesto del contributo della Santa Sede al bene dell’umanità

SOMMARIO: 1. La funzione e il ruolo della diplomazia pontificia nella Comunità internazionale - 2. Le dimensioni dell’attività diplomatica della Santa Sede dal pontificato di Giovanni Paolo II a quello di Francesco - 3. Il riconoscimento dei diritti umani nella diplomazia di Papa Francesco - 4. A servizio della pace nel mondo - 5. Libertà religiosa, cooperazione per il bene comune e promozione della persona umana - 6. Annotazioni conclusive. Diplomacy of the Holy See and the International Community In the context of the Holy See’s contribution to the good of mankind ABSTRACT: The article takes into consideration the reasons and purposes for the presence of the ‘supreme governing body of the Catholic Church’ in the international Community. The author reflects on the relationship between the diplomatic activity of the Holy See and the delicate issues of peace and war. Therefore, attention is given to the methods of intervention put in place by Pope Francis with reference to the protection of fundamental human rights. In fact, from the pontificate of Paul VI, to those of John Paul II and Benedict XVI, to even the present pontificate of Francis, the juridical and geo-political questions concerning peace and terrorism, war and nuclear disarmament, the defense of religious freedom and the improvement of universal relations between states, the reform of international organizations and the promotion of human rights have strongly characterized the modus agendi of the two thousand year-old papal diplomacy. Faced with these questions, the Holy See seems to confirm both its own sui generis international juridical subjectivity and its own ‘positive neutrality’ by means of a significant work of mediation in offering universally shared solutions to protect the ontological, irrepressible dignity of the human person

Inducers of epithelial mesenchymal transition and cancer stem cells in malignant pleural effusions

The Epithelial to Mesenchymal Transition (EMT) plays a role not only in tumor metastasis but also in tumor recurrence. This process is believed to be tightly linked to the presence of Cancer Stem Cells (CSCs) however, it is still not clear which factors could induce EMT and how it could be a source for CSCs. It has been demonstrated that Malignant Pleural Effusion (MPEs) may represent an excellent source to identify markers and molecular mechanisms involved in EMT and CSCs development. Growth factors, cell differentiation markers and molecular adhesion are involved in some of the crucial neoplastic cell events such as proliferation, metastasis, resistance to chemotherapy and EMT. In this review, we summarize the current understanding of which molecular markers can orchestrate EMT and CSCs in MPEs

Rapid on-site evaluation (ROSE) in pancreatic cancer diagnosis. doing more with less

Rapid on-site evaluation (ROSE) in pancreatic cancer diagnosis: Doing more with les

Clinical-pathological features of an occult mixed mucinous male breast cancer. a case report

Mucinous carcinoma of the male breast is an uncommon malignant breast neoplasm and its diagnoses remain difficult. It is probably due to such a low rate of breast cancer cases that men tend to be diagnosed at an older age than women and with a later stage of the disease. We describe a case of a 69-year-old male who displayed a palpable lump in his right axilla several years ago, showing signs of cutaneous adnexal mucinous adenocarcinoma after biopsy. After six years and several clinical examination and systemic investigation without results, the patient underwent to fine needle aspiration cytology and subsequently a biopsy of a mass with irregular margins in the retroareolar region of his right breast. The final diagnosis was of a mixed mucinous breast cancer with neuroendocrine differentiation. The tumor cells phenotype showed Synaptophisin (+), CEA (+/-), CK-20 (-), CK-7 (+), TTF-1 (-), estrogen receptor (-), progesterone (-) and HER 2 (++). These results were unusual for a mucinous male breast carcinoma. In the presence of a lesion in the axillary area with no specific primary origin, breast cancer should never be ruled out, even in the absence of clinical evidence and with an immunohistochemical pattern not indicative of mammary origin

Prognostic role of intragastric cytopathology and microbiota in surgical patients with stomach cancer

In the last decade, analysis of malignant cells and flora in gastric lavage (GL) has provided interesting data on pathogenesis of gastric cancer (GC). For this study, combining such two aspects into one cyto-microbiologic category, we tested the prognostic role of the presence/absence of cancer cells (GL1/GL0) and bacterial microbiota (MB1/MB0) in our GC population. Material and Methods: Between April 2012 and August 2019, 79 surgical patients with GC were prospectively investigated with the determination of GL MB. Results: Compared with GL1 MB0, GL1 MB1 strongly correlated with advanced GC, portended poorer overall survival (OS) (45.8 months vs 20.5 months, P = 0.049), and resulted a significant (P = 0.008) and an independent (P = 0.013) prognostic factor unfavorable for OS. Conclusion: In the light of our results, the cyto-microbiologic parameter of GL MB should be used to gain a better prognosis of GC patients. Administration of antimicrobial treatment for MB1 subjects should be entertained because it could reduce the risk of oncogenesis

Tissue inhibitor of metalloproteinase 2 (TIMP-2) expression in adenocarcinoma pleural effusions

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Human lung adenocarcinoma cell cultures derived from malignant pleural effusions as model system to predict patients chemosensitivity

BACKGROUND: Lung cancer is the leading cause of cancer related deaths and Malignant Pleural Effusion (MPE) is a frequent complication. Current therapies suffer from lack of efficacy in a great percentage of cases, especially when cancer is diagnosed at a late stage. Moreover patients' responses vary and the outcome is unpredictable. Therefore, the identification of patients who will benefit most of chemotherapy treatment is important for accurate prognostication and better outcome. In this study, using malignant pleural effusions (MPE) from non-small cell lung cancer (NSCLC) patients, we established a collection of patient-derived Adenocarcinoma cultures which were characterized for their sensitivity to chemotherapeutic drugs used in the clinical practice. METHODS: Tumor cells present in MPEs of patients with NSCLC were isolated by density gradient centrifugation, placed in culture and genotyped by next generation sequencing. In a subset of cases patient derived xenografts (PDX) were obtained upon tumor cell inoculation in rag2/IL2 knock-out mice. Isolated primary cultures were characterized and tested for drug sensitivity by in vitro proliferation assays. Additivity, antagonism or synergy for combinatorial treatments were determined by analysis with the Calcusyn software. RESULTS: We have optimized isolation procedures and culture conditions to expand in vitro primary cultures from Malignant Pleural Effusions (MPEs) of patients affected by lung adenocarcinomas, the most frequent form of non small cell lung cancer. Using this approach we have been able to establish 16 primary cultures from MPEs. Cells were banked at low passages and were characterized for their mutational pattern by next generation sequencing for most common driver mutations in lung cancer. Moreover, amplified cultures were shown to engraft with high efficiency when injected in immunocompromised mice. Cancer cell sensitivity to drugs used in standard chemotherapy regimens was assessed either individually or in combination. Differential chemosensitivity and different mutation profiles were observed which suggests that this isolation method could provide a platform for predicting the efficacy of chemotherapy in the clinical setting. Most importantly for six patients it was possible to establish a correlation between drug response in vitro and response to therapy in the clinic. CONCLUSIONS: Results obtained using primary cultured cells from MPEs underscore the heterogeneity of NSCLC in advanced stage as indicated by drug response and mutation profile. Comparison of data obtained from in vitro assays with patients' responses to therapy leads to the conclusion that this strategy may provide a potentially useful approach for evaluating individual chemosensitivity profile and tailor the therapy accordingly. Furthermore, combining MPE-derived primary cultures with their genomic testing allows to identify patients eligible to trials with novel targeted agents

IL-10, IL-13, Eotaxin and IL-10/IL-6 ratio distinguish breast implant-associated anaplastic large-cell lymphoma from all types of benign late seromas

Breast implant-associated anaplastic large-cell lymphoma (BI-ALCL) is an uncommon peripheral T cell lymphoma usually presenting as a delayed peri-implant effusion. Chronic inflammation elicited by the implant has been implicated in its pathogenesis. Infection or implant rupture may also be responsible for late seromas. Cytomorphological examination coupled with CD30 immunostaining and eventual T-cell clonality assessment are essential for BI-ALCL diagnosis. However, some benign effusions may also contain an oligo/monoclonal expansion of CD30 + cells that can make the diagnosis challenging. Since cytokines are key mediators of inflammation, we applied a multiplexed immuno-based assay to BI-ALCL seromas and to different types of reactive seromas to look for a potential diagnostic BI-ALCL-associated cytokine profile. We found that BI-ALCL is characterized by a Th2-type cytokine milieu associated with significant high levels of IL-10, IL-13 and Eotaxin which discriminate BI-ALCL from all types of reactive seroma. Moreover, we found a cutoff of IL10/IL-6 ratio of 0.104 is associated with specificity of 100% and sensitivity of 83% in recognizing BI-ALCL effusions. This study identifies promising biomarkers for initial screening of late seromas that can facilitate early diagnosis of BI-ALCL

Spheres Derived from Lung Adenocarcinoma Pleural Effusions: Molecular Characterization and Tumor Engraftment

Malignant pleural effusions (MPEs) could represent an excellent source to culture a wide variety of cancer cells from different donors. In this study, we set up culture conditions for cancer cells deriving from MPEs of several patients affected by the most frequent form of lung cancer, namely the subset of non small cell lung cancers (NSCLC) classified as Lung Adenocarcinomas (AdenoCa) which account for approximately 40% of lung cancer cases. AdenoCa malignant pleural effusions gave rise to in vitro cultures both in adherent and/or in spheroid conditions in almost all cases analyzed. We characterized in greater detail two samples which showed the most efficient propagation in vitro. In these samples we also compared gene profiles of spheroid vs adherent cultures and identified a set of differentially expressed genes. Finally we achieved efficient tumor engraftment in recipient NOD/SCID mice, also upon inoculation of small number of cells, thus suggesting indirectly the presence of tumor initiating cells

Collecting duct carcinoma of the kidney: an immunohistochemical study of 11 cases

BACKGROUND: Collecting duct carcinoma (CDC) is a rare but very aggressive variant of kidney carcinoma that arises from the epithelium of Bellini's ducts, in the distal portion of the nephron. In order to gain an insight into the biology of this tumor we evaluated the expression of five genes involved in the development of renal cancer (FEZ1/LZTS1, FHIT, TP53, P27(kip1), and BCL2). METHODS: We studied eleven patients who underwent radical nephrectomy for primary CDC. All patients had an adequate clinical follow-up and none of them received any systemic therapy before surgery. The expression of the five markers for tumor initiation and/or progression were assessed by immunohistochemistry and correlated to the clinicopathological parameters, and survival by univariate analysis. RESULTS: Results showed that Fez1 protein expression was undetectable or substantially reduced in 7 of the 11 (64%) cases. Fhit protein was absent in three cases (27%). The overexpression of p53 protein was predominantly nuclear and detected in 4 of 11 cases (36%). Immunostaining for p27 was absent in 5 of 11 cases (45.5%). Five of the six remaining cases (90%) showed exclusively cytoplasmic protein expression, where, in the last case, p27 protein was detected in both nucleus and cytoplasm. Bcl2 expression with 100% of the tumor cells positive was observed in 4 of 11 (36%) cases. Statistical analysis showed a statistical trend (P = 0.06) between loss and reduction of Fez1 and presence of lymph node metastases. CONCLUSIONS: These findings suggest that Fez1 may represent not only a molecular diagnostic marker but also a prognostic marker in CDC